The present invention relates to a method for attenuating sympathetic nervous system hyperactivity or onset of migraine by the sublingual, buccal or intranasal administration of selectively metabolized beta-blocking agents.
Sympathetic nervous system activation can result in heart rate or blood pressure increases. Activities causing such a result can be physical exertion such as climbing, running or sexual intercourse. Likewise, symptoms such as sweating, tremor and palpitations can result from short-term stressful conditions which might be caused, for example, by "stage fright" because of public speaking, vocal or musical performance or phobias.
Control of heart rate or blood pressure during short-term activities is particularly important for patients at risk due to coronary artery disease such as myocardial ischemic disorders. Severe attacks of chest pain, angina pectoris, occur when cardiac work and myocardial oxygen demand exceed the ability of the coronary arterial system to supply oxygen. The major determinants of myocardial oxygen consumption are heart rate, systolic tension or arterial pressure. Any increase in any of these determinants in the presence of reduced coronary blood flow may induce angina. The higher the blood pressure and the faster the heart rate, the greater the unmet myocardial oxygen need.
Likewise, sympathetic nervous system activation is also an important component of anxiety states in which patients complain primarily of bodily symptoms. These symptoms include palpitations, tremor, difficulty in breathing, sweating, flushing and dizziness. Such anxiety states include: acute stress disorders, as occur from short-term stressful conditions referred to as "stage fright" as in public speaking, vocal or musical performance or examinations; social phobias and panic disorders. Control of bodily symptoms associated with these conditions can alleviate the anxiety state in such patients.
Various drugs have been used to modulate cardiac work in patients with angina pectoris, including vasodilators and beta blockers. Beta blockers are also used in chronic treatment and prophylaxis of anxiety and migraine.
Nitroglycerin is the most commonly used vasodilator to treat angina. It is available in a number of different forms: sublingual tablets that dissolve under the tongue; sublingual sprays; chewable tablets; tablets and capsules for oral administration; ointments and patches for topical administration and solutions for intravenous administration. For treating sudden attacks of angina, the sublingual tablets and sprays and some chewable tablets are most effective. The other nitroglycerin dosage forms, and other nitrate medications, are generally used on a chronic basis to prevent angina attacks from occurring.
Beta blockers such as propranolol are available for chronic treatment and prophylaxis of angina and for other disease states requiring chronic attenuation of sympathetic nervous system hyperactivity, as well as for chronic prophylaxis of migraine. Only one drug, esmolol, is used for acute treatment of sympathetic hyperactivity by intravenous infusion in a hospital setting. These methods possess significant drawbacks for acute prevention or treatment of sympathetic hyperactivity because: prolonged duration of beta blocking action results in greater likelihood of adverse effects in susceptible individuals, such as those with bronchial disease or in diabetes; onset of action may be too slow; chronic beta blocker administration is costly and subjects patients to chronic, undesirable pharmacological actions and the intravenous dosage route is impractical for out of hospital use. Accordingly, there is a need for a method of treatment of acute sympathetic nervous system hyperactivity using beta-blocking agents which are conveniently administered, rapid acting, and have a relatively short duration of action.
Disclosed is a method for administration of selectively metabolized beta-blocking agents to a patient in need of such treatment to attenuate sympathetic nervous system activity or migraine. The method utilizes sublingual, buccal or intranasal administration of such compounds.